GCM is an underdiagnosed inflammatory myocardial disease all over the world. It has often been diagnosed after death or heart transplantation (5, 6).
Although GCM is known as a rare myocardial disease but its incidence has been reported 0.2% to 5% in EMB based myocarditis (7, 8).
GCM is commonly happening at young and middle-aged adults (1, 9).
In our series, the mean age of patients is 44.3 years that all of whom are women. These characteristics are consistent with previous studies (3, 6, 10).
The main clinical presentation of GCM is progressive heart failure (64% - 75%). Other clinical manifestations are high grade A-V block (5% - 31%), ventricular arrhythmia (VT-VF) (14% - 32%), acute coronary like syndromes (6% - 19%) (1, 6, 9, 11).
Approximately 20% of GCM cases have autoimmune disorders such as collagen vascular disease, thyroiditis or inflammatory bowel disease (12).
In our cases, the common symptoms were VT (occurring in three patients), CHB (the second case), heart failure (the second case).
Clinical diagnosis of GCM especially for middle aged woman should be suspected in the approach to a patient with ventricular arrhythmia and high grade A-V block even without significant LV dysfunction. Importance of GCM differential diagnosis especially with AVB is cardiac sarcoidosis (13, 14).
There are limited data on the use of non-invasive imaging such as cardiac MR and nuclear imaging (15). CMR was done in two of our cases which other than myocardial edema, in the first case, CMR showed a thick layer of myocardial late gadolinium enhancement (LGE) that was extended from sub epicardial to intramural LV. The third patient had LGE (sub endocardium) in inferolateral LV.
A recent report, compared CMR with histology in GCM, in which strain-encoded CMR showed a patchy distribution of LGE affecting all layers of myocardium (15).
Table 1 illustrates diagnostic importance of common imaging modalities in specific myocarditis (15).
Table 1.
Kadkhodayan et al. (15)
Imaging Modality | CMR | Echocardiography | Nuclear Imaging (18F-FDG PET) |
---|
Cardiac sarcoidosis | + | ++ | +++ |
Giant cell myocarditis | + | + | + |
Eosinophilic myocarditis | ++ | ++ | - |
Lymphocytic myocarditis | + | + | + |
Although non-invasive imaging cannot provide a definite distinction between inflammatory cardiomyopathy, but those are (especially CMR) standard references for initial and complementary assessment of myocardial tissue characterization and function (16).
EMB and histologic examination is the gold standard method for the diagnosis of GCM (17). The giant cells are the main characteristic feature of GCM (12). The classic histopathologic view of GCM are diffused myocyte necrosis with inflammatory cell infiltration including eosinophils, lymphocytes, multinucleated giant cells, plasma cells and neutrophils (9, 12, 18, 19).
The major differential diagnosis of GCM in histopathology are other myocardial lesion containing giant cells including sarcoidosis, infectious granulomatosis myocarditis, giant cell arteritis and Takayasu’s arteritis (4, 20).
Myocardial histopathology of the third case revealed giant cells with asteroid body but her imaging and clinical feature did not suggest cardiac sarcoidosis (CS). The pathologic characteristic features of CS to differentiate from GCM include non-necrotizing granuloma with giant cell and intracytoplasmic inclusions such as Schaumann and asteroid bodies (21).
However, the third case has been following for CS presentation. Our second case showed massive myocardial necrosis and severe inflammatory cells infiltration. With due attention to her very poor prognosis, it is possible to consider the relationship between myocardial pathologic view and clinical prognosis.
The simultaneous presence of parvovirus B19 genome and GCM can show triggering effect of parvovirus B19 infection on giant cell myocarditis (22).
There are no sufficient data management and follow up GCM (23). Kandolin et al. reported that 26 biopsy GCM diagnosed patients were treated with combined immunosuppression that included steroid (all patients), cyclosporine, mycophenolate mofetil, muromonab, gamma globulin and methotrexate. This report described that two third of patients partially recovered from severe clinical heart failure but continued the susceptibility to ventricular arrhythmia (6).
Five patients (total mortality) died due to ventricular arrhythmia. Twenty-five patients received beta-blocker (6).
Several other reports described the efficacy of immunosuppression therapy such as steroid, muromonab, cyclosporin, anti-thymocyte globulin (ATG) and mycophenolate mofetil that can be effective in relative clinical remission of GCM (9, 11, 24, 25).
Our first case was treated with steroid and MMF that achieved partial remission for ventricular arrhythmia.
In the second case, RV and LV functions were relatively recovered with steroid pulse and MMF.
The third patient was improved in the view of myocardial function and ventricular arrhythmia. Of course, arrhythmia ablation has been performed for her. However, it is clear that immunosuppressant drugs can partially control clinical heart failure and arrhythmia (7).
Further research specially clinical trials are required for drug combinations.
Anti heart-failure drugs (angiotensin-converting enzyme or angiotensin receptor blockers and B-blockers) have been used for our patients according to guidelines (26).
Specific guideline does not exist for re-biopsy in GCM to diagnose and follow up of the treatment and to estimate prognosis (2) but considering the results of the third-case re-biopsy, it is advisable to further research for re-biopsy and left ventricular biopsy in patients with GCM.
3.1. Conclusion
It is important to consider especially giant cell myocarditis in tachyarrhythmia and bradyarrhythmia with unknown origin, in particular for young and middle aged patients. Altogether, immunosuppressants can help to manage GCM, but clinical trials are necessary.
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